Department of Orthopedics, University Medical Center Utrecht, Utrecht, The Netherlands.
Developmental Bioengineering, University of Twente, Enschede, The Netherlands.
J Tissue Eng Regen Med. 2021 Jul;15(7):648-659. doi: 10.1002/term.3218. Epub 2021 May 21.
Meniscus regeneration could be enhanced by targeting meniscus cells and mesenchymal stromal cells (MSCs) with the right growth factors. Combining these growth factors with the Collagen Meniscus Implant (CMI®) could accelerate cell ingrowth and tissue formation in the implant and thereby improve clinical outcomes. Using a transwell migration assay and a micro-wound assay, the effect of insulin-like growth factor-1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-β1), fibroblast growth factor, and platelet lysate (PL) on migration and proliferation of meniscus cells and MSCs was assessed. The formation of extracellular matrix under influence of the above-mentioned growth factors was assessed after 28 days of culture of both MSCs and meniscus cells. As a proof of concept, the CMI® was functionalized with a VEGF binding peptide and coated with platelet-rich plasma (PRP) for clinical application. Our results demonstrate that PDGF, TGF-β1, and PL stimulate migration, proliferation, and/or extracellular matrix production of meniscus cells and MSCs. Additionally, the CMI® was successfully functionalized with a VEGF binding peptide and PRP which increased migration of meniscus cell and MSC into the implant. This study demonstrates proof of concept of functionalizing the CMI® with growth factor binding peptides. A CMI® functionalized with the right growth factors holds great potential for meniscus replacement after partial meniscectomy.
通过将正确的生长因子靶向半月板细胞和间充质基质细胞(MSCs),可以增强半月板再生。将这些生长因子与胶原半月板植入物(CMI®)结合使用,可加速细胞向内生长和植入物中的组织形成,从而改善临床结果。通过 Transwell 迁移测定和微划痕测定,评估了胰岛素样生长因子-1、血小板衍生生长因子(PDGF)、血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)、成纤维细胞生长因子和血小板裂解物(PL)对半月板细胞和 MSCs 迁移和增殖的影响。在培养 MSCs 和半月板细胞 28 天后,评估了上述生长因子影响下细胞外基质的形成。作为概念验证,用 VEGF 结合肽对 CMI®进行功能化,并涂覆富含血小板的血浆(PRP)用于临床应用。我们的研究结果表明,PDGF、TGF-β1 和 PL 刺激半月板细胞和 MSCs 的迁移、增殖和/或细胞外基质的产生。此外,CMI® 成功地用 VEGF 结合肽和 PRP 进行了功能化,这增加了半月板细胞和 MSC 向植入物中的迁移。这项研究证明了用生长因子结合肽对 CMI®进行功能化的概念验证。用正确的生长因子功能化的 CMI®在半月板部分切除后进行半月板置换具有巨大的潜力。